System for filling and assembling pharmaceutical delivery devices

ABSTRACT

The present invention provides for an assembly for filling and capping a barrel of a pre-filled syringe. The assembly includes a syringe body having a neck end, a rimmed end, and a side wall extending between the neck end and rimmed end. The body has an outer surface and an inner surface. The assembly includes a piston having an upper surface, a lower surface, and a side surface extending between the upper and lower surfaces. The inner surface of the body and the side surface of the piston is in contact to form a liquid impermeable seal. The assembly further includes a stabilization member that at least partially surrounds and contacts the outer surface of the body. The stabilization member is positioned proximate the rimmed end of the body to provide additional mass thereto in an amount sufficient to permit the assembly to be conveyed freestanding in a longitudinally upright position on the stabilization member through an apparatus for filling and capping pharmaceutical vials. Methods for producing a pre-filled syringe barrel are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-pending patentapplication Ser. No. 09/993,299, filed on Nov. 23, 2001.

FIELD OF THE INVENTION

This invention relates to the production of prefilled syringes for usein medical or veterinary treatment.

BACKGROUND OF THE INVENTION

Prefilled disposable syringes have gained wide acceptance as a preferreddosage form for administration of medicaments, primarily for reasons ofsafety and convenience. Most importantly, prefilled syringes minimizehandling of a medicament prior to administration, thereby reducing thechance of dosage errors or contamination of the medicament.

Many different types of prefilled disposable syringes have beendeveloped. Most known prefilled syringes include an elongate syringe“cartridge” or “barrel” comprising a cylindrical glass or plasticcontainer into which the medicament or a component thereof is prefilled.In some types of prefilled syringes, the barrel forms the body of asyringe, having a mouth which permits attachment to an injection needle,and a movable bottom comprising an elastomeric piston which is actedupon by a plunger to administer the medicament.

One common problem with prefilled disposable syringes is that adedicated filling and capping line is usually required to fill themedicament into the syringe barrel. This problem has previously beenaddressed by the invention described in European Patent No. 298,585,which describes a system for producing prefilled syringe barrels onordinary equipment for filling and capping pharmaceutical vials. Thatpatent describes a system whereby the syringe barrel is made shorter andwider than a conventional barrel, so that it has the shape of a standardpharmaceutical vial, and is then filled and capped on standard machineryfor filling and capping vials, through which the barrels are conveyedwhile standing on their bases. Since the pharmaceutical vial is astandardized container which is widely used in the pharmaceuticalindustry, most pharmaceutical companies have existing vial fillingequipment. The equipment need only be modified by the addition of astation for insertion of the rubber piston into the body of the barrel.Therefore, the invention described in that prior patent eliminates theneed for specialized filling equipment, thereby reducing cost.

Despite the improvements described in the applicant's above-mentionedEuropean patent, the further disadvantage exists that the relativelysquat vial-shaped barrels cannot be used in all types of deliverysystems. Some delivery systems, such as syringe pumps and two componentsystems, may require the use of conventional, elongate barrels whichcannot be filled on standard vial-filling equipment. Therefore, it wouldbe advantageous to provide a system which allows the preparation ofconventional, elongate prefilled syringe barrels on standard equipmentfor filling and capping pharmaceutical vials.

SUMMARY OF THE INVENTION

The one aspect, the present invention provides for an assembly forfilling and capping a barrel of a pre-filled syringe comprising:

-   -   a) a syringe body having a neck end, a rimmed end, and a side        wall extending between the neck end and rimmed end, the body        having an outer surface and an inner surface;    -   b) a piston having an upper surface, a lower surface, and a side        surface extending between the upper and lower surfaces, the        inner surface of the body and the side surface of the piston in        contact to form a liquid impermeable seal; and    -   c) a stabilization member that at least partially surrounds and        contacts the outer surface of the body, the stabilization member        is positioned proximate the rimmed end of the body to provide        additional mass thereto in an amount sufficient to permit the        assembly to be conveyed freestanding in a longitudinally upright        position on the stabilization member through an apparatus for        filling and capping pharmaceutical vials.

In a further aspect, the stabilization member comprises a sleeve, thesleeve has a top end and a base end, and the rimmed end of the body ispositioned within the sleeve proximate the base end of the sleeve.

In still a further aspect, the base end of the sleeve has a radiallyprojecting flange.

In yet a further aspect, the flange has a substantially flat outwardlyfacing wall that is substantially vertical when the assembly is standinglongitudinally upright.

In still a further aspect, the stabilization member further comprises astabilization cap having a hollow portion with an upper end and a lowerend, the lower end having a finger flange that extends radiallyoutwardly therefrom, the hollow portion is sized to closely fit withinthe body, and the finger flange is sized to fit within the base end ofthe sleeve.

In yet a further aspect, the piston comprises a material that isimpermeable to liquid and sufficiently permeable to a sterilizing gas topermit sterilization of the seal between the inner surface of the bodyand the side surface of the piston upon exposure to a sterilizing gas.

In still a further aspect, the piston comprises neoprene.

In yet a further aspect, the piston comprises a material that issubstantially resistant to the effects of at least one standard cycle ofgamma radiation.

In still a further aspect, the piston comprises bromo-butyl rubber.

In yet a further aspect, the syringe body comprises cerium oxide in anamount sufficient to prevent discoloration of the body upon exposure toat least one standard cycle of gamma radiation.

In still a further aspect, the syringe body comprises about 1 wt %cerium oxide based on the total weight of the syringe body.

In a second aspect, the present invention provides a method forproducing a barrel for a pre-filled syringe, comprising:

-   -   a) providing a syringe body having a neck end, a rimmed end, and        a side wall extending between the neck end and rimmed end, the        body having an outer surface and an inner surface;    -   b) providing a piston having an upper surface, a lower surface,        and a side surface extending between the upper and lower        surfaces;    -   c) providing a stabilization member; and    -   d) forming an assembly comprising the syringe body, the piston,        and the stabilization member such that: (i) the inner surface of        the body contacts at least a portion of the side surface of the        piston to form a liquid impermeable seal; (ii) the stabilization        member at least partially surrounds and contacts the outer        surface of the body; and (iii) the stabilization member is        positioned proximate the rimmed end of the body to provide        additional mass thereto in an amount sufficient to permit the        assembly to be conveyed freestanding in a longitudinally upright        position on the stabilization member through an apparatus for        filling and capping pharmaceutical vials.

In a further aspect, the syringe body provided in step (a) ispre-sterilized, the piston provided in step (b) is pre-sterilized, andthe stabilization member provided in step (c) is pre-sterilized andsteps (a)-(d) are performed in an aseptic environment.

In still a further aspect, the method further comprises, subsequent tostep (d), the step of (e) overwrapping the assembly with an overwrapmaterial in an aseptic environment to maintain sterility.

In yet a further aspect, the method further comprises, subsequent tostep (e), the steps of:

-   -   f) removing the overwrap;    -   g) filling the body with at least one pharmaceutical component        through the neck end using the apparatus for filling and capping        pharmaceutical vials; and    -   h) capping the neck end of the body using the apparatus for        filling and capping pharmaceutical vials.

In still a further aspect, the at least one pharmaceutical component isin the form of a solid when filled into the body.

In yet a further aspect, the at least one pharmaceutical component is inthe form of a liquid when filled into the body.

In still a further aspect, the method further comprises, subsequent tostep (g) and prior to step (h), the step of lyophilizing the at leastone pharmaceutical.

In yet a further aspect, the method further comprises, prior to step(b), the step of selecting a material for the piston that is impermeableto liquid but sufficiently permeable to a sterilizing gas to permitsterilization of the seal between the inner surface and the body and theside surface of the piston upon exposure to a sterilizing gas.

In still a further aspect, the method further comprises, subsequent tostep (d), the step of (e) overwrapping the assembly with an overwrapmaterial.

In yet a further aspect, the method further comprises, subsequent tostep (e), the step of (f) sterilizing the barrel with a sterilizing gas.

In still a further aspect, the method further comprises, prior to step(b), the step of selecting a material for the piston that issufficiently resistant to at least one cycle of gamma radiation.

In yet a further aspect, the method further comprises, prior to step(a), the step of selecting a material for the syringe body material thatcomprises cerium oxide in an amount sufficient to prevent discolorationof the body upon exposure to at least one cycle of gamma radiation.

In still a further aspect, the method further comprises, subsequent tostep (d), the step of (e) overwrapping the assembly with an overwrapmaterial.

In yet a further aspect, the method further comprises, subsequent tostep (e), the step of (f) sterilizing the barrel with at least one cycleof gamma radiation.

In a third aspect, the present invention provides a method for producinga pre-filled syringe barrel, comprising:

-   -   a) providing a sterile assembly comprising a syringe body having        a neck end, a rimmed end, a side wall extending between the neck        end and the rimmed end, an outer surface and an inner surface, a        piston having an upper surface, a lower surface, and a side        surface extending between the upper and lower surfaces and a        stabilization member, the sterile assembly formed such that: (i)        the inner surface of the body contacts at least a portion of the        side surface of the piston to form a liquid impermeable        seal; (ii) the stabilization member is at least partially        surrounds and contacts the outer surface of the body; and (iii)        the stabilization member is positioned proximate the rimmed end        of the body to provide additional mass thereto in an amount        sufficient to permit the assembly to be conveyed freestanding in        a longitudinally upright position on the stabilization member        through an apparatus for filling and capping pharmaceutical        vials;    -   b) filling the body with at least one pharmaceutical component        through the neck end using the apparatus for filling and capping        pharmaceutical vials; and    -   c) capping the neck end of the body using the apparatus for        filling and capping pharmaceutical vials.

In a further aspect, the method further comprises, prior to step (b),the step of maintaining the assembly in an aseptic environment until itis ready to be filled through the neck end of the body with the at leastone pharmaceutical component.

In still a further aspect, steps (b) and (c) are performed in an asepticenvironment.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described, by way of example only, byreference to the accompanying drawings in which:

FIG. 1 schematically illustrates a method for preparing a prefilledsyringe barrel according to a first preferred embodiment of the presentinvention;

FIG. 2 illustrates the lower portion of the syringe barrel of FIG. 1prior to insertion of the piston into the body;

FIG. 3 illustrates the lower portion of the syringe barrel of FIG. 1after insertion of the piston into the body;

FIG. 4 schematically illustrates a variant of the method shown in FIG. 1in which the syringe barrels are packaged in trays for sterilization;

FIG. 5 schematically illustrates a variant of the method shown in FIG. 1in which the body is filled with a powder;

FIG. 6 schematically illustrates a variant of the method shown in FIG. 1in which the body is filled with a freeze-dried medicament;

FIG. 7 illustrates combination of the syringe barrel of the firstpreferred embodiment with other components to form a delivery device fora two component medicament;

FIG. 8 schematically illustrates a method for preparing a prefilledsyringe barrel according to a second preferred embodiment of the presentinvention;

FIG. 9 schematically illustrates a variant of the second preferredembodiment in which a plurality of piston supports and sleeves aresecured to a handling tray;

FIG. 10 schematically illustrates another variant of the secondpreferred embodiment in which a plurality of piston supports are securedto a handling tray;

FIG. 11 illustrates a variant of the syringe barrel according to thesecond preferred embodiment of the present invention;

FIG. 12 illustrates a further variant of the syringe barrel according tothe second preferred embodiment of the present invention;

FIG. 13 illustrates a further variant of the syringe barrel according tothe second preferred embodiment of the present invention;

FIG. 14 illustrates a variant of the syringe barrel according to thefirst preferred embodiment of the present invention; and

FIG. 15 illustrates a variant of the syringe barrel according to thefirst or second preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

A first preferred embodiment of the invention will now be discussedbelow in the context of a syringe barrel which is intended for use in adelivery device for a two component medicament. Such a delivery deviceis described in U.S. Pat. No. 6,149,623, issued on Nov. 21, 2000 whichis incorporated herein by reference in its entirety.

FIG. 1 illustrates a preferred sequence of steps to be followed duringpreparation of a prefilled syringe barrel 10 for use in a two componentdelivery device. The illustrations of the syringe barrel shown in FIG. 1are somewhat schematic. Details of the lower portions of the syringebarrel 10 are more clearly shown in FIGS. 2 and 3.

The barrel 10 comprises a body 12 preferably made of glass and having agenerally cylindrical side wall 14 with an inner surface 16 and an outersurface 18. At one end, the body 12 has a relatively narrow neck 20 witha neck flange 21 surrounding an open mouth 22, and at the other end thebody 12 has an open rimmed end 24. Although the lower end of the body 12is referred to herein as the “rimmed end”, it is to be appreciated thatthe body 12 may or may not have a perceptible inwardly or outwardlyextending rim or flange at its lower edge.

The body 12 illustrated in FIG. 1 has a height to base ratio ofapproximately 4.5:1. It will be appreciated that the present inventioncan be utilized with barrels of various dimensions, including barrelshaving greater height to base ratios than that shown in FIG. 1, andbarrels having lower height to base ratios, such as the vial-shapedbarrels previously described which generally have height to base ratiosnot exceeding 2.5:1.

Barrel 10 further comprises a generally cylindrical elastomeric piston26 having an upper surface 28 which forms the bottom wall of the barrel10 in its assembled state, and an opposed lower surface 30 with aninternally threaded bore (not shown). Piston 26 also has a side surface32 connecting the upper and lower surfaces 28 and 30, the side surface32 being adapted to form a hermetic seal with the inner surface 16 ofbody 12, and preferably being provided with one or more ribs 34 toimprove the seal with the body 12. Piston 26 is preferably made from anelastomeric material such as rubber.

The open mouth 22 of body 12 is sealed in a conventional manner by anelastomeric closure 36 with an overlying metal cap 38 crimped over theneck flange 21.

Barrel 10 is also provided with an activation cap 40 at its rimmed end24, the cap 40 performing a number of functions which are describedbelow. As best seen in FIGS. 2 and 3, activation cap 40 comprises agenerally cylindrical sleeve 42 having a base end 44 and a top end 46,the rimmed end 24 of body 12 being received inside the top end 46 ofsleeve 42 in a close fit with the rimmed end 24 being locatedintermediate the top end 46 and the base end 44 of the sleeve 42 (bestseen in FIG. 2).

Preferably, the sleeve 42 has an inwardly projecting portion 48extending radially inwardly from the inner wall of the sleeve 42. Theinwardly projecting portion 48 shown in FIG. 1 comprises a detent ofsufficient shape and size to retain the rimmed end 24 of the syringebody 12 intermediate the top end 46 and the base end 44 of the sleeve 42in the absence of a force which pushes the rimmed end 24 of the body 12and the base end 44 of the sleeve 42 toward one another, but whichpermits the rimmed end 24 to be pushed toward the base end 44 inresponse to a predetermined force, such as a downward force applied tothe body 12 when the barrel 10 is standing upright on the base end 44 ofthe sleeve 42. As defined herein, a detent includes any inwardprojection of the sleeve 42 which is effective to retain the rimmed ends24 of the body 12, including a continuous circumferential lip or one ormore protrusions, as shown in FIGS. 1 to 3, on the inner surface of thesleeve 42.

The activation cap 40 further comprises piston support means 50including a piston support surface 52 on which the piston 26 issupported such that its upper surface 28 is spaced from the rimmed end24 of the body 12 (shown in FIG. 2), thereby providing a gap 54 betweenthe piston 26 and the body 12 which permits exposure of substantiallythe entire piston 26 and body 12 to a sterilizing gas as discussed belowin greater detail. Furthermore, the piston 26 is supported such that itis substantially concentric with the rimmed end 24 of the body 12, readyfor insertion into the rimmed end 24 of the body 12.

In the preferred embodiment of FIG. 1, the piston support means 50 is incontact with the sleeve 42 and is integrally formed therewith, bothbeing components of the activation cap 40. As best seen in FIGS. 1 and2, the piston support surface 52 is positioned radially inwardly of theinner surface of the sleeve 42. Preferably, the piston support surface52 is spaced inwardly from the inner surface of the sleeve 42 by adistance which is substantially equal to the thickness of the body sidewall, thereby forming an annular recess 56 between the piston supportsurface 52 and the inner surface of the sleeve 42. The annular recess 56has a bottom wall 58 connecting the piston support means 50 and thesleeve 42 and located intermediate the piston support surface 52 and thelower surface of the base end 44 of the sleeve 42, such that when apredetermined force is applied to push the rimmed end 24 of the body 12into the annular recess 56 until the rimmed end 24 engages the bottomwall 58, the piston 26 becomes fully inserted in the body 24 with itsside surface 32 forming a hermetic seal with the inner surface 16 of thebody 12.

In order to permit engagement of piston 26 by a plunger, the pistonsupport surface 52 is annular with a central aperture 64, and engages anouter edge of the lower surface 30 of the piston 26. In the embodimentillustrated in FIGS. 1 to 3, the piston is preferably provided with athreaded bore (not shown) open to its lower surface 30 which is adaptedfor connection to the threaded end of a plunger.

As discussed above, the system of the invention is adapted to improvethe stability of conventional, elongate syringe barrels, therebypermitting them to be conveyed standing upright through standardequipment for filling and capping pharmaceutical vials. This object ispartly attained by provision of the sleeve 42, which may lower thecentre of gravity of the barrel 10 somewhat, thereby improving itsstability. Stability can be further enhanced by increasing the thicknessof the sleeve 42 throughout part or all of its height. For example, asshown in FIG. 1, the sleeve 42 may preferably be provided with anoutwardly projecting flange 66 at its base end 44. The flange 66 has adiameter and a height so as to prevent interference such as would causetipping when the barrel 10 is conveyed standing upright on the base end44 through standard equipment for filling and capping pharmaceuticalvials. Such interference typically comprises a phenomenon known as“shingling”, in which the flange or one barrel rides up over the flangeof another barrel, resulting in tipping.

Shingling can be prevented as shown in the preferred embodiment of FIG.1, in which the flange 66 has a substantially flat radially outwardlyfacing wall 68 and is of sufficient height that the flanges 66 ofadjacent barrels 10 will not ride up over one another.

FIG. 1 illustrates the steps involved in assembling and filling a barrel10 with a liquid component of a medicament, which may comprise an activeingredient or a diluent to be combined with an active ingredient priorto administration.

The first step of the method, illustrated in FIG. 1 a, comprises theformation of a first assembly 70 by inserting the piston 26 inside thesleeve 42 of activation cap 40 such that the lower surface 30 of piston26 is supported by the piston support surface 52.

In the second step illustrated in FIG. 1 b, a second assembly 72 (shownin FIG. 1 c) is formed by inserting the rimmed end 24 of body 12 intothe top end 46 of sleeve 42 to a sufficient depth that the body 12 isstably supported in the sleeve 42, and so that the rimmed end 24 islocated intermediate the top end 46 and the base end 44 of the sleeveand gap 54 being formed between the upper surface 28 of piston 26 andthe rimmed end 24 of the body 12, thereby permitting sterilization ofthe body 12, piston 26 and activation cap 40 by a sterilizing gas. Aclose-up cross-sectional view of the lower portion of second assembly 72is shown in FIG. 2.

The next step in the method, schematically illustrated in FIG. 1 dcomprises sterilization of the second assembly 72 by a sterilizing gassuch as steam or ethylene oxide. FIG. 4 schematically illustrates avariant of the method in which the sterilization is performed while aplurality of assemblies 72 are packaged in trays 73 and covered with aplastic overwrap 75 so as to maintain sterility and keep them in place.A preferred plastic overwrap is sold under the trade-mark TYVEK™, whichmaintains sterility while allowing penetration of sterilizing gases suchas ethylene oxide.

After sterilization, a force is applied to the second assembly 72 tocause relative movement of the body 12 toward the base end 44 of thesleeve 42, thereby causing insertion of the piston 26 into the body 12such that the side surface 32 of the piston 26 forms a hermetic sealwith the inner surface 16 of the body 12 and seals the rimmed end 24.Preferably, the body 12 is pushed downward into sleeve 42 in thedirection shown by the arrow in FIG. 1 e. This step may be performedwhile the assemblies 72 are packaged in trays 73 and covered with theoverwrap 75. Alternatively, the overwrap 75 may preferably be removedfrom the sterile assemblies 72 (preferably in a sterile environment)prior to pushing the body 12 into sleeve 42, and the assemblies 72 maypreferably also be removed from the tray 73 prior to performing thisstep. The sterile tray of assemblies may be shipped to a location forfilling, stored for future filling, or immediately filled with apharmaceutical component. In the first two situations, preferably thetray 73 and assemblies 72 are maintained in the overwrap 75 until theyare to be filled, thus maintaining them in a sterile environment.

With the piston 26 fully inserted in the body 12 as shown in FIG. 1 e,and shown in greater detail in FIG. 3, the body 12 is now ready to befilled with a medicament, or a component thereof. In this embodiment,the medicament is a liquid which is filled into the open mouth 22 of thebody 12. As discussed above, the body 12 is filled on standard equipmentfor filling and capping pharmaceutical vials, and is conveyed through atleast part of said equipment freestanding on the base end 44 of sleeve42. The filled body 12 is illustrated in FIG. 1 f.

The mouth 22 of the body 12 is then sealed in a conventional manner byapplication of an elastomeric closure 36 as shown in FIG. 1 g, followedby application of a metal cap 38 over the closure 36 as shown in FIG. 1h, the cap 38 preferably being crimped over the neck flange 21 of thebody 12. This is also the most common method for sealing standardpharmaceutical vials and is therefore easily performed on standardequipment for filling and capping pharmaceutical vials.

The next step in the method is illustrated in FIG. 1 i and comprises anoptional terminal sterilization step, in which the sealed barrel 10 issubjected to sterilization, for example by exposure to high temperaturesin an autoclave. This step is also part of the normal vial fillingprocess and is performed on standard equipment for filling and cappingpharmaceutical vials.

As mentioned above, the barrel 10 of the first preferred embodimentcomprises an activation cap 40 and is therefore specifically directed todelivery devices for two component pharmaceuticals. In the exampledescribed above, a liquid medicament, or a liquid component of amedicament, is contained in the barrel 10. However, the first preferredembodiment is also adaptable to the situation where the barrel 10contains a solid medicament or a solid component of a medicament, whichis to be combined with a liquid, such as a diluent, prior toadministration.

A first preferred method for filling barrel 10 with a solid medicamentis illustrated in FIG. 5. The steps followed in FIG. 5 are preferablythe same as those described above with reference to FIG. 1, with theexception of step 5 f, in which a powdered substance is filled into body12 through the mouth 22. Powder filling is also performed on standardequipment for filling and capping pharmaceutical vials.

A second preferred method for filling barrel 10 with a solid medicamentis illustrated in FIG. 6. FIGS. 6 a to 6 e show preparation of thesecond assembly 72, followed by sterilization and seating of the piston26 in the barrel body 10. These steps are identical to the stepsfollowed in FIGS. 1 a to 1 e, discussed above. Next, the body 12 isfilled in FIG. 6 f with a liquid composition containing a medicament ora component thereof. This step is identical to that shown in FIG. 1 f.Next, a lyophilization stopper 74, comprising a vented elastomericclosure, is partially inserted into the neck 20 of body 12 such that avent space 76 is formed. The liquid contents of the body 12 are thenlyophilized as shown in FIG. 6 g such that only a solid remains in thebody 12. The stopper 74 is then completely inserted into neck 20 toclose vent space 76 and seal the body, and a metal cap 38 is applied asin FIG. 1 h. Although not shown in FIG. 6, the sealed barrel may besubjected to terminal sterilization. The steps shown in FIGS. 6 f to 6 iare performed on standard equipment for filling, lyophilizing andcapping pharmaceutical vials.

As mentioned above, the barrel 10 according to the first preferredembodiment is capable of use in a two component delivery device, such aspreferred delivery device 78 shown in FIG. 7 b. In order to assembledelivery device 78, the barrel 10 is combined with a pre-assembly 80 ofthe type illustrated in FIG. 7 a, comprising a standard pharmaceuticalvial 82 having a sealed neck 84, a vial coupling 86 with a vial socket88 into which the neck 84 of vial 82 is received, and a syringe socket90 with a finger flange 91 into which the barrel 10 is received.

The pre-assembly further comprises a rear needle 93 and a forward needle94 housed in a luer lock assembly 96 which is secured to both the vialcoupling 86 and the syringe socket 90. When the delivery device 78 isassembled as in FIG. 7 b with the finger flange 92 engaging the top end46 of activation cap 40, the ends of needles 93 and 94 do not penetratethe elastomeric closures of either the vial 82 or the barrel 10. Thedevice 78 is activated by pushing the syringe socket 90 and theactivation cap 40 together such that the sleeve 42 of cap 40 is receivedinside syringe socket 90. The socket 90 and cap 40 are pushed togetheruntil the finger flange 92 engages the flange 66 of activation cap 40,at which point the ends of needles 93 and 94 penetrate the closures ofthe barrel 10 and the vial 82 respectively, allowing mixing of therespective contents of the vial 82 and barrel 10, in this example byattaching plunger 98 to the piston 26 and aspirating the liquid contentsof the vial 82 into the barrel 10. The vial coupling 86 is thenunthreaded from the luer 96, also removing the forward needle 94. Aninjection needle (not shown) is then threaded onto the exposed luer 96to provide a complete prefilled disposable syringe (not shown). Thecomponents of pre-assembly 80, and the method for combining barrel 10and pre-assembly 80 are described in greater detail in above-mentionedU.S. Pat. No. 6,149,623, which is incorporated herein by reference inits entirety. It will be appreciated that the activation cap 40described herein functions in a manner similar to the driver describedin the above-mentioned U.S. patent and identified by reference numeral21 in FIGS. 17 and 18 thereof.

Where the barrel 10 contains a liquid medicament or a component thereof,the vial 82 of pre-assembly 80 may comprise either a solid or liquid.Where the vial 82 contains a solid, the medicament is formed by pushingthe liquid contents of barrel 10 into the vial 82, mixing the solid andliquid ingredients, followed by aspirating the medicament suspension orsolution into the barrel 10 prior to removal of the vial coupling 86.

A second preferred embodiment of the present invention is now describedbelow with reference to FIG. 8, comprising preparation of a barrel 110for use in the preparation of a prefilled disposable syringe foradministration of a single component medicament. A barrel similar tobarrel 110 is shown in FIG. 13 of U.S. Pat. No. 5,137,511, issued onAug. 11, 1992, and is incorporated herein by reference in its entirety.

Barrel 110 comprises a body 112 preferably made of glass and having agenerally cylindrical side wall 114 with an inner surface 116 and anouter surface 118. At one end, the body 112 has a relatively narrow neck120 with a neck flange 121 surrounding an open mouth 122, and at theother end the body 112 has an open rimmed end 124. Preferably, therimmed end 124 is provided with an inwardly extending projection 125which has a function to be described below. The dimensions of body 112are similar to those of body 12 described above, although it will beappreciated that the dimensions of body 112 can be varied as discussedabove in the context of the first preferred embodiment.

Barrel 110 further comprises a generally cylindrical elastomeric piston126 having an upper surface 128 which forms the bottom wall of barrel110 in its assembled state, and an opposed lower surface 130. Piston 126also has a side surface 132 connecting the upper and lower surfaces 128and 130, the side surface 132 being adapted to form a hermetic seal withthe inner surface 116 of body 112, and preferably being provided withone or more ribs 134 to improve the seal with the body 112. Piston 126is preferably made from an elastomeric material such as rubber. Thelower surface of piston 126 comprises an extension 139 for attachment toa plunger as described in greater detail in above-mentioned EuropeanPatent No. 298,585.

The open mouth 122 of body 112 is sealed in a conventional manner by anelastomeric closure 136 with an overlying metal cap 138 crimped over theneck flange 121.

The barrel 110 further comprises a stabilization cap 140 which has anumber of functions. Firstly, stabilization cap 140 functions as apiston support means, having a cylindrical portion 142 with an upper end144 and a lower end 146, the upper end having a piston support surface148. The outer diameter of the cylindrical portion 142 is such that thecylindrical portion 142 can be received inside the body 112. Thestabilization cap 140 also has a radially projecting flange 150 at itslower end which functions as a finger flange during use of the syringe.Furthermore, the cylindrical portion 142 of cap 140 has a radiallyinwardly recessed band 152 which is adapted to form a snap fit with theinwardly projecting portion 125 of the body side wall 114, therebypreventing removal of piston 126 from the body.

FIG. 8 illustrates the steps involved in assembling and filling a barrel110 with a liquid component of a medicament. The first step, illustratedin FIG. 8 a, comprises placement of the piston 126 on top of the pistonsupport surface 148 of the stabilization cap 140, such that theextension 139 of piston 126 is received inside the cylindrical portion142, which is of sufficient height that the extension 139 does notcontact the surface on which the stabilization cap 140 is supported.

The next step comprises placement of a cylindrical sleeve 154 over thepiston 126 and cap 140 as illustrated in FIG. 8 b. The cylindricalsleeve 154 performs a function similar to that of sleeve 42 ofactivation cap 40 described above, namely to add stability to the barrel110 and to support the body 112 in spaced relation to the piston 126during initial assembly of the barrel 110. In contrast to sleeve 42 ofcap 40, the cylindrical sleeve 154 does not form part of the barrel 110,but rather is removed after filling and capping of the barrel 110 onstandard equipment for filling and capping pharmaceutical vials. As withsleeve 42, the cylindrical sleeve 154 can further enhance stability ofthe barrel 110 by being increased in thickness, by providing a flangesimilar to flange 66 of cap 40 and/or by forming the sleeve 154 from arelatively dense material, such as stainless steel. Since the sleeve 154is removed from the barrel, preferably for re-use, forming the sleevefrom a relatively thick and/or dense material does not add to the weightor cost of the barrel.

As shown in FIG. 8, it may be preferred to form the sleeve with apartial recess 156 in its lower surface 158 to fit over the flange ofthe stabilization cap 140, thereby substantially centering the piston126 within the sleeve 154 and preventing relative movement between thesleeve 154 and the cap 140.

After combining the piston 126, stabilization cap 140 and sleeve 154 toform a first assembly 160 as shown in FIG. 8 c, the body 112 is insertedinto the top end of the sleeve 154 to form a second assembly 162, withthe body 112 being inserted into the sleeve 154 to a sufficient depththat the body 112 is stably supported therein and so that the rimmed end124 of the body 112 is supported intermediate the top end of sleeve 154and the flange 150 of the stabilization cap 140.

Preferably, the inner surface of the sleeve 154 is provided with adetent 164 which prevents premature insertion of the piston 126 into thebody 112, as discussed in detail with reference to the first preferredembodiment.

The next step of the method, illustrated in FIG. 8 d, comprisessterilization of the second assembly 162 by a sterilizing gas. As in thefirst preferred embodiment, a plurality of assemblies 162 may preferablybe packaged in trays with a plastic overwrap prior to sterilization.After sterilization, the piston 126 is inserted into the body 112 bypushing the body 112 downward relative to sleeve 154 in the direction ofthe arrow shown in FIG. 8 e until the inward projection 125 of body 112snaps into the recess 152 of the stabilization cap.

The steps followed for filling, capping and terminal sterilization ofthe sealed body 112 are shown in FIGS. 8 e to 8 i and are identical tothe corresponding steps followed in FIGS. 1 e to 1 i. As with the firstpreferred embodiment, these steps are performed on standard equipmentfor filling and capping pharmaceutical vials, with the sealed body 112and the associated sleeve 154 being conveyed through at least a portionof this equipment while freestanding upright on the finger flange 150.

After removal of the sleeve 154, the barrel 110 can be combined with aneedle (not shown) and a plunger (not shown) to form a prefilleddisposable syringe, as described in above-mentioned U.S. Pat. No.5,137,511.

FIGS. 9 and 10 illustrate variants of the second preferred embodiment ofthe invention in which components of the system are attached to trays.In the variant shown in FIG. 9, prefilled syringe barrels 168 areproduced by combining a body 12 or 112 with a piston 126 having anextension 139. The barrels 168 include neither an activation cap 40 or astabilization cap 140 and are therefore similar to pharmaceutical vials,although they may preferably have a greater height to base ratio thanstandard pharmaceutical vials.

In the variant shown in FIG. 9, a handling tray 170 is provided on whichare arranged a plurality of support assemblies 172, each of whichcomprises a generally cylindrical sleeve 174 having a base end 175 and atop end 177, and piston support means 176 integrally formed with thesleeve 174 and having an annular piston support surface 178 adapted tosupport piston 126 by engaging the lower surface 130 thereof. A planview of tray 170 with support assemblies 172 is shown in FIG. 9 d. As inthe first embodiment shown in FIGS. 1 to 3, piston support surface 178is spaced from the inner surface of sleeve by a distance substantiallyequal to a thickness of the wall of the body 12 or 112 to form anannular gap 180 into which the rimmed end of the body 12 or 112 isreceived during insertion of the piston 126 into the body 12 or 112.

In order to assemble syringe barrels 168, the pistons 126 are firstinserted into the support assemblies 172 as shown in FIG. 9 a andsupported on the piston support means 176. Next, the bodies 12 or 112are inserted into the sleeves 174 as shown in FIG. 9 b and supportedtherein with their rimmed ends spaced above the upper surfaces 128 ofthe pistons 126. In order to support the bodies 12 or 112 in theposition shown in FIG. 9 c, the inner surface of each sleeve 174 ispreferably provided with a detent (not shown) as described above in thecontext of sleeve 42 and 154. After sterilization, the pistons 126 arethen inserted into the bodies 12 or 112 by pushing the bodies 12 or 112downward such that the rimmed ends thereof are pushed down into the gaps180 (FIGS. 9 c and 9 e), as described above in connection with the firstpreferred embodiment illustrated in FIG. 1.

After insertion of the pistons 126, the trays 170 and the barrels 168are conveyed through equipment adapted for filling syringe barrelspackaged in trays. After filling, the barrels 168 are sealed and cappedas described above, preferably while standing on the trays 170. Thefilled and capped barrels 168 may then be removed from trays 170 priorto shipment, with the trays being reused. Alternatively, the tray 170and barrels 168 may be shipped as a unit to their final destination.

FIG. 10 illustrates a variant of the method of FIG. 9, in which trays182 are provided with piston support means 184 attached thereto. A planview of the tray is shown in FIG. 10 a. As shown in FIGS. 10 b and 10 c,pistons 139 are placed on the support means. The bodies 12 or 112 areinserted into an assembly 186 comprising a plurality of sleeves 188joined together, the inner surface of each sleeve 188 having a detent(not shown) to support the rimmed end of the body 12 or 112 as shown inFIG. 10 d. After insertion of bodies 12 or 112 into sleeves 188 as shownin FIG. 10 d, the assembly 186 is placed over the tray 182 so that apiston support means 184 and an associated piston is inserted into eachsleeve 188 as shown in FIG. 10 e. After sterilization, the pistons 126are inserted into bodies 12 or 112 as shown in FIG. 10 e, therebyproviding a tray of sterilized barrels shown in FIG. 10 f, ready forfilling and capping as described above with reference to FIG. 9.

FIG. 11 illustrates a variant of the second preferred embodiment inwhich a syringe barrel 192 is produced by combining a body 12 or 112with a piston 26 having an internally threaded bore. As in the variantshown in FIGS. 9 and 10, the variant of FIG. 11 does not include anactivation cap 40 or a stabilization cap 140. In the variant of FIG. 11,the barrel 192 is stabilized on standard equipment for filling andcapping vials by a stabilization means 194 comprising a sleeve 196 andan integrally formed piston support means 198 comprising an annularpiston support surface 200 and having a raised central portion 201 to bereceived in the bore of the piston 26, thereby centering the pistoninside the sleeve 196. The sleeve 196 is provided with a plurality ofaxially extending, circumferentially spaced support ribs 195, best seenin FIG. 11 d, which is a cross-sectional plan view showing thestabilization means 194 in isolation, the cross-section being taken in aplane perpendicular to the axis of sleeve 196 and between the detents202 and the piston support means 198. As shown in FIG. 11 a, each rib195 is provided with a detent 202 on its inner surface for supportingthe body 12 or 112 above the upper surface 28 of the piston.

To produce a prefilled syringe barrel 192, the piston 26 is firstinserted into the stabilization means as shown in FIG. 11 a. Next, thebody 12 or 112 is inserted into the sleeve 196 as shown in FIG. 11 buntil the rimmed end engages the detents 202 on ribs 195 as shown inFIG. 11 c. It is to be noted that only stabilization means 194 is shownin cross-section in FIGS. 11 a to 11 c, with the other components beingshown in elevation. The remaining steps are analogous to those shown inFIG. 8, with the exception that, after the barrel 192 is filled andcapped, it is pulled out of engagement with the stabilization means 194.

FIG. 12 also illustrates a variant of the second preferred embodiment,and is similar to the variant of FIG. 11, with the exception that it isadapted for forming a syringe barrel comprising a body 12 or 112 and apiston 126 having an extension 139. As in FIG. 11, the embodiment ofFIG. 12 utilizes a stabilization means 190 comprising a sleeve 191 and apiston support means 193, the sleeve 191 having a plurality of axiallyextending ribs 197, each of which is provided with a detent 199. FIG. 12a illustrates the subassembly of the piston 126 and the stabilizationmeans 190 prior to insertion of body 12 or 112. FIG. 12 b illustratesbody 12 or 112 having been inserted into sleeve 191 and being supportedby detent 189, such that a gap exists between the rimmed end of the body12 and the upper surface of piston 126. In FIGS. 12 a and 12 b, only thestabilization means 190 is shown in cross section, with the othercomponents being shown in elevation. FIG. 12 c is a cross-sectional planview showing the stabilization means in isolation, in a plane which isperpendicular to the axis of sleeve 191, and which is between thedetents 199 and piston support means 193.

FIG. 13 illustrates yet another variant of the second preferredembodiment, which is similar to that illustrated in FIG. 8 except thatpiston 126 is replaced by piston 26 having an internal bore, and sleeve154 is replaced by sleeve 203, having axially extending ribs 205, eachof which is provided with a detent 207. As shown in FIG. 13 b, ribs 205terminate immediately below detent 207. FIG. 13 a illustrates piston 26being placed on stabilization cap 204, comprising a cylindrical portion206 with a flange 208 at the base end thereof, the flange 208 serving asa finger flange. Stabilization cap 204 also comprises a recessed band210 adapted to snap into engagement with the inwardly projecting portion125 at the rimmed end 124 of body 112. FIG. 13 b illustrates theplacement of the cylindrical sleeve 203 over the piston 26 and thestabilization means 204 to form the assembly 212 shown in FIG. 13 c.FIG. 13 c also shows insertion of the insertion of body 112 into sleeve203 to form the assembly 213 shown in FIG. 13 d, which is ready forsterilization and further processing according to the method describedin connection with FIG. 8. FIGS. 13 a to 13 d illustrate the sleeve 203in cross section and the other components in elevation. FIG. 13 a is across-sectional plan view showing the sleeve 203 in isolation, taken ina plane extending through ribs 205 and perpendicular to the axis ofsleeve 203.

FIG. 14 illustrates a variant of the first preferred embodiment of thepresent invention, identical to that shown in FIGS. 1 to 3 except thatbody 214 replaces syringe body 12. Body 214 has a rimmed edge 216 withslight outward projection 218 and a slight inward projection 220. FIG.14 a is analogous to FIG. 2 and illustrates an assembly comprising thebody 214, piston 26 and activation cap 40 prior to insertion of piston26 into body 214. FIG. 14 b is analogous to FIG. 3 and illustrates theassembly of FIG. 14 a after the body 214 has been pushed down intoactivation cap 40, and piston 26 is inserted into body 214.

FIG. 15 illustrates a variant that may be implemented with either thefirst or second preferred embodiments of the invention, but forconvenience will be described having reference to the first preferredembodiment shown in FIG. 1. In addition to the body, piston, sleeve, andother components previously described in reference to FIG. 1, thevariant shown in FIG. 15 includes an upper cylindrical sleeve 250. Theupper cylindrical sleeve 250 has an upper end 252, a lower end 254, andinner surface 256 and an outer surface 258. The interior diameter of theupper sleeve 250 is such as to closely, but not tightly, surround thebody of the syringe barrel. Preferably, the outer diameter of the uppersleeve 250 is approximately the same as the outer diameter of the sleeve42. The upper sleeve may have an outer collar 260, having an innersurface 262 and an outer surface 264, the collar 260 surrounding atleast a portion of the upper sleeve 250. The inner surface 262 of thecollar 260 preferably has a greater diameter than the outer surface 258of the upper sleeve 250 thereby creating an annular gap 266 between theupper sleeve 250 and the collar 260. Preferably the collar 260 has anopen bottom end 268 towards the lower end 254 of the sleeve 250, and aclosed end 270 towards the upper end 252 where the collar 260 has thesame outer diameter as the flange 66 of the base end 44 of the sleeve42. After the barrel is filled with a pharmaceutical component, theupper sleeve 250 may be removed before packaging and shipment, andreused. For example, the upper sleeve 250 may be removed by blasting airinto the annular gap 266, causing the upper sleeve to blow off the topof the barrel.

The inclusion of the upper sleeve may increase the stability of thebarrels as they travel through a filling line, since the upper collar260 and the flange 66 are preferably of the same diameter. Thus, ifadjacent barrels traveling through the filling line contact one another,they will do so at the flange 66 near the base of the barrel, and alsoat the collars 260. This will increase the stability of the barrels asthey travel through the filling line.

It will be appreciated that the activation caps, stabilization caps,sleeves and handling trays described above will preferably be made frommaterials which are substantially unaffected by the conditions employedduring sterilization. As sterilization is usually performed at elevatedtemperature, it is preferred that these components be made ofheat-resistant materials. It is preferred that these components beformed from plastics, more preferably heat-resistant plastics.

Furthermore, it may be preferred in some embodiments of the presentinvention to utilize syringe bodies and pistons which are siliconized.Siliconization is preferably performed during manufacture of the syringebody and the piston.

In one aspect, the present invention provides an assembly for fillingand capping a barrel 10 of a pre-filled syringe. The assembly generallyhas a syringe body 12, a piston 26, and a stabilization member. Thestabilization member is positioned proximate the rimmed end of the bodyto provide additional mass thereto in an amount sufficient to permit thebarrel 10 to be conveyed freestanding in a longitudinally uprightposition on the stabilization member through an apparatus for fillingand capping pharmaceutical vials. In essence, the stabilization memberacts to lower the center of gravity of the barrel 10 while the barrel 10is in a longitudinally upright position (see FIGS. 1 e, 4 f, 5 e 6 e, 8e, and 9 e). This permits the stable conveyance of the assembly throughan apparatus for filling and capping pharmaceutical vials. In theembodiment illustrated in FIGS. 1-7, the stabilization member is sleeve42. In the embodiment illustrated in FIG. 8, the stabilization memberincludes sleeve 154 and stabilization cap 140. In the embodimentillustrated in FIG. 9, the stabilization member is sleeve 174. In theembodiment illustrated in FIG. 11, the stabilization member is sleeve196. In the embodiment illustrated in FIG. 12, the stabilization memberis sleeve 191. In the embodiment illustrated in FIG. 13, thestabilization member includes sleeve 203 and stabilization cap 204.

The following description is a variant on the method steps forassembling and filling a barrel with at least one pharmaceuticalcomponent in accordance with either the first or the second preferredembodiments of the invention. For convenience, the method variant willbe described having reference to FIG. 1.

The syringe body 12, piston 26, and sleeve 42 can be pre-sterilized inany method known in the art. The pre-sterilized syringe body 12, thepre-sterilized piston 26, and the pre-sterilized sleeve 42 can beassembled in an aseptic environment to form the assembly shown in FIG. 1e. While in this position, the piston 26 is located within the body 12so that a liquid impermeable seal is formed between the inner surface 16of the body 12 and the side surface 34 of the piston 26. Preferably, theassembly shown in FIG. 1 e is packaged in a plastic overwrap sold underthe trade-mark TYVEK™ while still in the aseptic environment.Preferably, the assembly is maintained in the sterile packaging until itis ready to be filled. It is understood that the subsequent steps forfilling and capping can be identical to the corresponding stepspreviously described depending on the state of the at least onepharmaceutical component to be filled (e.g., FIGS. 1 f to 1 i or FIGS. 8f to 8 j for filling an assembly with at least one liquid pharmaceuticalcomponent, FIGS. 5 f to 5 i for filling an assembly with at least onesolid pharmaceutical, FIGS. 6 f to 6 j for filling an assembly with atleast one liquid pharmaceutical followed by lyophilization such thatonly a solid remains).

The following description is a variant on the method steps forassembling and filling a barrel with at least one pharmaceuticalcomponent in accordance with either the first or the second preferredembodiments of the invention. For convenience, the method variant willbe described having reference to FIG. 1.

The syringe body 12, piston 26, and sleeve 42 can be assembled in arelatively clean room to form the assembly shown in FIG. 1 e. While inthis position, the piston is located within the body 12 so that a liquidimpermeable seal is formed between the inner surface 16 of the body 12and the side surface 34 of the piston 26. The material for the piston 26is selected to be liquid impermeable and sufficiently permeable to asterilizing gas to permit sterilization of the seal between the innersurface 16 of the body 12 and the side surface 34 of the piston 26 uponexposure to a sterilizing gas. The material for the piston 26 can beselected from any material that is known in the art to be liquidimpermeable and permeable to a sterilizing gas. Examples of suchmaterials include, but are not limited to, elastomer formulationscomprising neoprene (e.g., elastomer formulation FM-27 which iscommercially available from Helvoet Pharma). Preferably, the assemblyshown in FIG. 1 e is packaged in a plastic overwrap sold under thetrade-mark TYVEK™. The wrapped assembly can then be sterilized byexposure to a sterilizing gas such as ethylene oxide. Preferably, theassembly is maintained in the sterile packaging until it is ready to befilled. It is understood that the subsequent steps for filling andcapping can be identical to the corresponding steps previously describeddepending on the state of the at least one pharmaceutical component tobe filled.

The following description is a variant on the method steps forassembling and filling a barrel with at least one pharmaceuticalcomponent in accordance with either the first or the second preferredembodiments of the invention. For convenience, the method variant willbe described having reference to FIG. 1.

The syringe body 12, piston 26, and sleeve 42 can be assembled in arelatively clean room to form the assembly shown in FIG. 1 e. While inthis position, the piston is located within the body 12 so that a liquidimpermeable seal is formed between the inner surface 16 of the body 12and the side surface 34 of the piston 24. Preferably, the syringe body12 is selected from a material that comprises cerium oxide in an amountsufficient to prevent discoloration of the body upon exposure to atleast one standard cycle of gamma radiation (e.g., 25 kilogray).Preferably, the syringe body 12 comprises about 1 wt % cerium oxidebased on the total weight of the syringe body 12. The material for thepiston 26 is selected to be substantially resistant to the effects of atleast one standard cycle of gamma radiation (e.g., 25 kilogray) to theextent that the function of the piston 26 is not impaired. The materialfor the piston 26 can be selected from any material that is known in theart to be resistant to the effects of at least one standard cycle ofgamma radiation. Examples of such materials include, but are not limitedto, elastic formulations comprising bromobutyl rubber (e.g., elastomerfomulation FM-457 which is commercially available from Helvoet Pharma).Preferably, the assembly shown in FIG. 1 e is packaged in a plasticoverwrap sold under the trade-mark TYVEK™. The wrapped assembly can thenbe sterilized by exposure to at least one standard cycle of gammaradiation (e.g., 25 kilogray). Preferably, the assembly is maintained inthe sterile packaging until it is ready to be filled. It is understoodthat the subsequent steps for filling and capping can be identical tothe corresponding steps previously described depending on the state ofthe at least one pharmaceutical component to be filled.

Although the invention has been described with reference to certainpreferred embodiments, it is not limited thereto. Rather, the inventionincludes all embodiments which may fall within the scope of thefollowing claims.

1. An assembly for filling and capping a barrel of a pre-filled syringe,the assembly comprising: a) a syringe body having a neck end, a rimmedend, and a side wall extending between the neck end and rimmed end, thebody having an outer surface and an inner surface; b) a piston having anupper surface, a lower surface, and a side surface extending between theupper and lower surfaces, the inner surface of the body and the sidesurface of the piston in contact to form a liquid impermeable seal; andc) a stabilization member that at least partially surrounds and contactsthe outer surface of the body, the stabilization member is positionedproximate the rimmed end of the body to provide additional mass theretoin an amount sufficient to permit the assembly to be conveyedfreestanding in a longitudinally upright position on the stabilizationmember through an apparatus for filling and capping pharmaceuticalvials.
 2. An assembly according to claim 1, wherein the stabilizationmember comprises a sleeve, the sleeve has a top end and a base end, andthe rimmed end of the body is positioned within the sleeve proximate thebase end of the sleeve.
 3. An assembly according to claim 2, wherein thebase end of the sleeve has a radially projecting flange.
 4. An assemblyaccording to claim 3, wherein the flange has a substantially flatoutwardly facing wall that is substantially vertical when the assemblyis standing longitudinally upright.
 5. An assembly according to claim 2,wherein the stabilization member further comprises a stabilization caphaving a hollow portion with an upper end and a lower end, the lower endhaving a finger flange that extends radially outwardly therefrom, thehollow portion is sized to closely fit within the body, and the fingerflange is sized to fit within the base end of the sleeve.
 6. An assemblyaccording to claim 1, wherein the piston comprises a material that isimpermeable to liquid and sufficiently permeable to a sterilizing gas topermit sterilization of the seal between the inner surface of the bodyand the side surface of the piston upon exposure to a sterilizing gas.7. An assembly according to claim 1, wherein the piston comprisesneoprene.
 8. An assembly according to claim 1, wherein the pistoncomprises a material that is substantially resistant to the effects ofat least one standard cycle of gamma radiation.
 9. An assembly accordingto claim 1, wherein the piston comprises bromo-butyl rubber.
 10. Anassembly according to claim 9, wherein the syringe body comprises ceriumoxide in an amount sufficient to prevent discoloration of the body uponexposure to at least one standard cycle of gamma radiation.
 11. Anassembly according to claim 9, wherein the syringe body comprises about1 wt % cerium oxide based on the total weight of the syringe body.
 12. Amethod for producing a barrel for a pre-filled syringe, comprising: a)providing a syringe body having a neck end, a rimmed end, and a sidewall extending between the neck end and rimmed end, the body having anouter surface and an inner surface; b) providing a piston having anupper surface, a lower surface, and a side surface extending between theupper and lower surfaces; c) providing a stabilization member; and d)forming an assembly comprising the syringe body, the piston, and thestabilization member such that: (i) the inner surface of the bodycontacts at least a portion of the side surface of the piston to form aliquid impermeable seal; (ii) the stabilization member at leastpartially surrounds and contacts the outer surface of the body; and(iii) the stabilization member is positioned proximate the rimmed end ofthe body to provide additional mass thereto in an amount sufficient topermit the assembly to be conveyed freestanding in a longitudinallyupright position on the stabilization member through an apparatus forfilling and capping pharmaceutical vials.
 13. A method according toclaim 12, wherein the syringe body provided in step (a) ispre-sterilized, the piston provided in step (b) is pre-sterilized, andthe stabilization member provided in step (c) is pre-sterilized andsteps (a)-(d) are performed in an aseptic environment.
 14. A methodaccording to claim 13, further comprising, subsequent to step (d), thestep of (e) overwrapping the assembly with an overwrap material in anaseptic environment to maintain sterility.
 15. A method according toclaim 14, further comprising, subsequent to step (e), the steps of: f)removing the overwrap; g) filling the body with at least onepharmaceutical component through the neck end using the apparatus forfilling and capping pharmaceutical vials; and h) capping the neck end ofthe body using the apparatus for filling and capping pharmaceuticalvials.
 16. A method according to claim 15, wherein the at least onepharmaceutical component is in the form of a solid when filled into thebody.
 17. A method according to claim 15, wherein the at least onepharmaceutical component is in the form of a liquid when filled into thebody.
 18. A method according to claim 17, further comprising, subsequentto step (g) and prior to step (h), the step of lyophilizing the at leastone pharmaceutical.
 19. A method according to claim 12, furthercomprising, prior to step (b), the step of selecting a material for thepiston that is impermeable to liquid but sufficiently permeable to asterilizing gas to permit sterilization of the seal between the innersurface and the body and the side surface of the piston upon exposure toa sterilizing gas.
 20. A method according to claim 19, furthercomprising, subsequent to step (d), the step of (e) overwrapping theassembly with an overwrap material.
 21. A method according to claim 20,further comprising, subsequent to step (e), the step of (f) sterilizingthe barrel with a sterilizing gas.
 22. A method according to claim 21,further comprising, subsequent to step (f), the steps of: g) removingthe overwrap; h) filling the body with at least one pharmaceuticalcomponent through the neck end using the apparatus for filling andcapping pharmaceutical vials; and i) capping the neck end of the bodyusing the apparatus for filling and capping pharmaceutical vials.
 23. Amethod according to claim 22, wherein the at least one pharmaceuticalcomponent is in the form of a solid when filled into the body.
 24. Amethod according to claim 22, wherein the at least one pharmaceuticalcomponent is in the form of a liquid when filled into the body.
 25. Amethod according to claim 24, further comprising, subsequent to step (h)and prior to step (i), the step of lyophilizing the at least onepharmaceutical.
 26. A method according to claim 12, further comprising,prior to step (b), the step of selecting a material for the piston thatis sufficiently resistant to at least one cycle of gamma radiation. 27.A method according to claim 26, further comprising, prior to step (a),the step of selecting a material for the syringe body material thatcomprises cerium oxide in an amount sufficient to prevent discolorationof the body upon exposure to at least one cycle of gamma radiation. 28.A method according to claim 27, further comprising, subsequent to step(d), the step of (e) overwrapping the assembly with an overwrapmaterial.
 29. A method according to claim 28, further comprising,subsequent to step (e), the step of (f) sterilizing the barrel with atleast one cycle of gamma radiation.
 30. A method according to claim 29,further comprising, subsequent to both steps (f) the steps of: g)removing the overwrap; h) filling the body with at least onepharmaceutical component through the neck end using the apparatus forfilling and capping pharmaceutical vials; and i) capping the neck end ofthe body using the apparatus for filling and capping pharmaceuticalvials.
 31. A method according to claim 30, wherein the at least onepharmaceutical component is in the form of a solid when filled into thebody.
 32. A method according to claim 30, wherein the at least onepharmaceutical component is in the form of a liquid when filled into thebody.
 33. A method according to claim 32, further comprising, subsequentto step (h) and prior to step (i), the step of lyophilizing the at leastone pharmaceutical.
 34. A method for producing a pre-filled syringebarrel, comprising: a) providing a sterile assembly comprising a syringebody having a neck end, a rimmed end, a side wall extending between theneck end and the rimmed end, an outer surface and an inner surface, apiston having an upper surface, a lower surface, and a side surfaceextending between the upper and lower surfaces and a stabilizationmember, the sterile assembly formed such that: (i) the inner surface ofthe body contacts at least a portion of the side surface of the pistonto form a liquid impermeable seal; (ii) the stabilization member is atleast partially surrounds and contacts the outer surface of the body;and (iii) the stabilization member is positioned proximate the rimmedend of the body to provide additional mass thereto in an amountsufficient to permit the assembly to be conveyed freestanding in alongitudinally upright position on the stabilization member through anapparatus for filling and capping pharmaceutical vials; b) filling thebody with at least one pharmaceutical component through the neck endusing the apparatus for filling and capping pharmaceutical vials; and c)capping the neck end of the body using the apparatus for filling andcapping pharmaceutical vials.
 35. A method according to claim 34,further comprising, prior to step (b), the step of maintaining theassembly in an aseptic environment until it is ready to be filledthrough the neck end of the body with the at least one pharmaceuticalcomponent.
 36. A method according to claim 35, wherein steps (b) and (c)are performed in an aseptic environment.
 37. A method according to claim36, wherein the at least one pharmaceutical component is in the form ofa solid when filled into the body.
 38. A method according to claim 36,wherein the at least one pharmaceutical component is in the form of aliquid when filled into the body.
 39. A method according to claim 38,further comprising, subsequent to step (b) and prior to step (c), thestep of lyophilizing the at least one pharmaceutical.